chr15-81273108-G-A

Variant names:

• chr15-81273108-G-A
• rs776826431
• NM_172217.5:c.694G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_172217.5(IL16):​c.694G>A​(p.Val232Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V232A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: IL16 NM_172217.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.44
• Publications: 0 publications found

Genes affected

IL16 (HGNC:5980): (interleukin 16) The protein encoded by this gene is a pleiotropic cytokine that functions as a chemoattractant, a modulator of T cell activation, and an inhibitor of HIV replication. The signaling process of this cytokine is mediated by CD4. The product of this gene undergoes proteolytic processing, which is found to yield two functional proteins. The cytokine function is exclusively attributed to the secreted C-terminal peptide, while the N-terminal product may play a role in cell cycle control. Caspase 3 is reported to be involved in the proteolytic processing of this protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172217.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	NM_172217.5	MANE Select	c.694G>A	p.Val232Ile	missense	Exon 6 of 19	NP_757366.2	Q14005-1
	IL16	NM_001352686.2		c.847G>A	p.Val283Ile	missense	Exon 6 of 19	NP_001339615.1
	IL16	NM_001438661.1		c.835G>A	p.Val279Ile	missense	Exon 6 of 19	NP_001425590.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL16	ENST00000683961.1	MANE Select	c.694G>A	p.Val232Ile	missense	Exon 6 of 19	ENSP00000508085.1	Q14005-1
	IL16	ENST00000302987.10	TSL:1	c.835G>A	p.Val279Ile	missense	Exon 6 of 19	ENSP00000302935.5	A0A8C8KBU6
	IL16	ENST00000909975.1		c.694G>A	p.Val232Ile	missense	Exon 6 of 19	ENSP00000580034.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000481 AC: 12 AN: 249532 AF XY: 0.0000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461008 Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23 AN XY: 726842

African (AFR) AF: 0.0000299 AC: 1 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39662

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111436

Other (OTH) AF: 0.0000332 AC: 2 AN: 60304

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74306

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000579 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	M
PhyloP100		8.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.18
Sift	Benign	0.035	D
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.50
MutPred		0.60		Loss of ubiquitination at K235 (P = 0.1423)
MVP		0.41
MPC		0.45
ClinPred		0.71	D
GERP RS		4.9
Varity_R		0.24
gMVP		0.37
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs776826431; hg19: chr15-81565449;